Prequalification team Regulatory capacity building and NDRA approvals of prequalified products Milan Smid Prequalification team Microbiological training, Nov 2011, Jordan

Principal objective of PQP capacity building: To facilitate availability of quality priority medicines Good quality submissions and compliance with "good practices" Strengthening of regulatory functions and fast approvals of PQd medicines Reliable quality monitoring PQP builds capacity in general: PQP technical expertise is used in support of capacity building of regulators, quality control laboratories and manufacturers WHO/PQP standards and PQP example support strengthening of regulatory systems and manufacturing capacity Focus on regulators in: Countries recipient PQ medicines Major producing countries without stringent regulation Other countries of specific need Map of regions – regulators and manufacturers/ QCLs

Capacity building resources All PQ team is involved Close co-operation with WHO colleagues, many collaborating organizations, pool of external experts Funding coming from several donors, especially UNITAID, BMGF, GFATM, UNCoLSP, USFDA … Stress: QSM: norms and standards, SSFFCs, regulatory support, pharmacovigilance experts from SRAs Microbiological training, Nov 2011, Jordan

Frequent partners in capacity building European Directorate for the Quality of Medicines & Healthcare (EDQM) International Pharmaceutical Federation (FIP) United Nations Population Fund (UNFPA) National Regulatory Authorities in UK, Canada, South Africa, Tanzania, Estonia, Ethiopia, Ukraine, Morocco, Brazil, Jordan, Ghana, Egypt, Indonesia, Kenya, Uganda, China National Quality Control Laboratories in Morocco and Tanzania East Africa Community (EAC) Association of Southeast Asian Nations (ASEAN) Ministry of Health China, Pakistan, Morocco Program for Appropriate Technology in Health (PATH) European Medicines Agency (EMEA) Drug Information Association (DIA) Therapeutic Goods Agency Australia (TGA) Roche Pharmaceuticals …………….. Benefits of collaboration with partnering organizations financial share share of workload More experts available Microbiological training, Nov 2011, Jordan

Key capacity building approaches 1) Training activities of different set-up 2) Technical assistance & consultancy 3) Provision of information, standards and regulatory expertise

Trainings: individualized and collective (seminars and workshops) Training of regulators integrated into core PQP activities NMRA assessors in PQ assessment NMRA inspectors in PQ inspections NMRAs professionals in quality monitoring of medicines Rotations of assessors and inspectors from NMRAs Joint problem solving Joint assessments Collaborative registrations Informal audits of manufacturers, QCLs and CROs with training effect Assessment sessions – each 2 months ? Assessors from developing countries Inspections – producing country and observers Data about rotations? 17 or 18 – mostly Afro Microbiological training, Nov 2011, Jordan

Seminars and workshops Frequent collaboration with third parties Microbiological training, Nov 2011, Jordan

Seminars and workshops Trainings of NRA staff and manufacturers frequently combined Microbiological training, Nov 2011, Jordan

Why trainings with combined audience of regulatory and regulated professionals? Need to combine objectives due to agreements with donors PQ of prioritized medicines is key PQT deliverable Common technical understanding needed by manufacturers and regulators Facilitation of communication On site problem solution Less expensive Easier to measure the outcome

Seminars and workshops General: PQ procedures and WHO requirements Technical, to reflect identified needs, e.g.: Product specific: HIV/AIDS, TB, antimalarial or RH products Pharmaceutical development/paediatric dosage forms Quality of APIs, Stability testing Manufacture of sterile medicines Bioequivalence testing and GCP Dissolution and water determination, microbiological testing, HPLC analyses, quality management system Microbiological training, Nov 2011, Jordan

Microbiological training, Nov 2011, Jordan

Provision of information and regulatory expertise Information related to individual PQ products or manufacturers /CROs http://www.who.int/prequal Product list and pending procedures Public assessment reports (WHOPAR, SPC, PIL) Public inspection reports (WHOPIR – APIs and FPPs) Notice of concern / suspension Guidelines and standards PQ laboratories Training materials Published training materials and standards / CDs Availability of non-WHO standards (Ph.Eur., ICH) Technical Briefing Seminars in Geneva Collaborative registration procedures

Support to rational regulation, development of regulatory systems, regulatory networking and worksharing Emerging projects: 'Prequalification' of key regulatory functions relevant for regulation of generic medicines Systematic development of competencies of regulatory professionals in areas relevant for regulation of generic medicines Pilot of distant learning approaches Microbiological training, Nov 2011, Jordan

WHO Collaborative Procedure to facilitate and accelerate registrations of prequalified medicines Procedure drafted in wide consultation and approved by WHO advisory expert committee in October 2012. Approved by WHO Executive Board in May 2013. Pilot ongoing from June 2012, currently 16 participating NMRAs from 15 countries. Africa Botswana Ethiopia Ghana Kenya Madagascar Mozambique Namibia Nigeria Tanzania Europe/Asia Georgia Kyrgyzstan Ukraine Uganda Zambia Zanzibar Zimbabwe www.who.int/prequal/info_applicants/collaborative_registration_main.htm Microbiological training, Nov 2011, Jordan

Principles of the process 1) Being asked by PQ holder (manufacturer), PQT shares full PQ assessment and inspection outcomes with NMRAs participating in the scheme and provides advice to facilitate national regulatory decisions (registrations, variations, withdrawals). - Applicable only for medicines assessed/inspected by PQP - PQ holder provides consent with information sharing - Voluntary for manufacturers and NMRAs and does not interfere with national decision making process and regulatory fees.

Principles of the process 2) It is up to discretion of participating NMRAs how to benefit from shared information. However, participating NMRAs commit to adopt registration decision within 90 days from having available full PQP assessment and inspection outcomes. NMRAs have the right to decline to adopt procedure for individual medicines decide differently from PQP, but keep PQP informed and clarify reasons for deviation.

Options for participating regulators Recognize Verify Organize R/B second review and/or inspections Consider in decision making Use as quality assurance of national assessment and decision

Outcomes of the process Product and registration dossier in countries are 'the same' as approved by PQP. Co-operation among PQP holder (manufacturer), NMRA in interested country and PQP is necessary to overcome confidentiality issues, assure information flow and product identity. 'Harmonized product status' is monitored and maintained Microbiological training, Nov 2011, Jordan

Steps of the procedure: registration PQ product is submitted for national registration to NMRA participating in the procedure NMRA is informed about the interest to follow PQP Manufacturer informs PQP about national submission and gives consent with information sharing Participating NMRA confirms its interest to participate in procedure for specific product PQP shares with participating NMRA outcomes of assessment and inspections Template documents for each step. Participating NMRA reviews WHO PQP outcomes, decides within 90 days decides upon the national registration and informs PQP about its decision Microbiological training, Nov 2011, Jordan

Experience with the procedure 20 procedures successfully terminated by registration in 7 countries: Ghana 5 Kenya 1 Zimbabwe 5 Uganda 1 Namibia 4 Nigeria 2 Tanzania 2 14 different prequalified products (9 ARVs, 1 RH, 1 antimalarial, 1 TB) 6 PQ holders involved, all from India

Number of finalized procedures according to time bands Days from accepting supportive PQ data to national registration

Percentage of finalized procedures according to time bands Days from accepting supportive PQ data to national registration

Learning and challenges What is 'the same product' ? Applicability for pending national registrations? Submissions of reduced registration dossiers in resource limited settings? Use of other languages than English? Quality control of registration samples? NMRAs administrative capacity and competence? Role of NMRAs and Drug Boards? Mednet as information system: suitable, but not optimal. Synchronization of national and PQ variations? Microbiological training, Nov 2011, Jordan

Win-win outcomes for all stakeholders Manufacturers Harmonized data for PQ and national registration Facilitated interaction with NMRAs in assessment and inspections Accelerated and more predictable registration Easier post-registration maintenance Procurers Faster start of procurement and wider availability of PQ medicines Assurance about 'the same' medicine as is prequalified (website)

Win-win outcomes for all stakeholders NMRAs Availability of WHO assessment and inspection outcomes to support national decisions and save internal capacities Opportunity to learn from PQP assessors and inspectors Demonstrating NMRA efficiency Having assurance about registration of 'the same' medicine as is prequalified Quality control by same methods and specifications Easier post-registration maintenance WHO Prequalified medicines are faster available to patients Feed-back on WHO prequalification outcomes

Newcomers to the network are welcome! Status Quo The collaborative registration of PQed medicines is in its infancy, but starts to produce results Procedure provides model for inter-regulatory information exchange to those NMRAs and manufacturers, who want to cooperate Extension of mechanism to SRA approved PQed products to be explored in co-operation with SRAs and manufacturers. Extension to 'originators' in principle not impossible. Newcomers to the network are welcome! Microbiological training, Nov 2011, Jordan

Zazibona – ‘look to the future’ (Zambian ‘nyanja’ language) Pilot of collaborative registration procedure in four mutually co-operating regulatory authorities Zambia, Zimbabwe, Botswana and Namibia Testing the applicability of collaboration in exchange of assessment and inspection reports on generic medicines (not submitted for WHO-PQP) among NMRAs in participating countries Not be involved in regulatory collaboration schemes demonstrates inefficiency and lack of professionalism Recent experience from assessment report sharing exercise Microbiological training, Nov 2011, Jordan

Zazibona - perspective Regulatory collaboration in exchange of assessment and inspection reports to reduce regulatory workload to accelerate registrations of needed products to develop mutual confidence in regulatory collaboration to test the mechanism of co-operation among regulatory authorities for potential use by others to improve information sharing and/or networking. Current focus on registration assessment Microbiological training, Nov 2011, Jordan

Zazibona – enabling factors No language barriers and geographically close Partially overlapping pharmaceutical markets All meeting capacity constraints and fighting backlog of applications Agencies/ministries able to adopt necessary decisions All members of SADC and having good contacts among themselves Having semi-harmonized guidelines and similar speed in implementation of international standards Co-operating with PQP and participating in PQP collaborative registration procedure Differences in interpretation can be bigger than differences in guidelines themsekves – in the bacgroung Who-(PQP) and SADC guidelies Current focus on registration assessment, but inspections, maintenance, QC and PhV later … Microbiological training, Nov 2011, Jordan

Agreed steps Agreement of HoA backed by MoH on pilot of mutual collaboration Several meetings of assessors to support AR sharing and develop experience BE (comparator, sourcing, BW) and stability conditions DMFs, pharmacopoeias, product information, communication platform Meeting with inspectors to agree on exchange of inspection reports and inspection planning Regular interaction among assessors, inspectors and HoA to cultivate joint work Similar issues like IGDRP , EU multistate procedures … CTD, ARs WHO/PQP model Differences in standards not considered essential, with exception of – BE (compartor and its sourcing and BW) and stability! DMFs, Product information, pharmacopoeias parked to future. A Not priority To ne overcome – IT tool – Mednet, Microbiological training, Nov 2011, Jordan

Summary Capacity building of national regulators is core PQP agenda integrated into all PQP activities PQP capacity building is not isolated agenda, reacts on identified needs and focuses on technical competence Scope of capacity building is influenced by priorities of donors, but also reflects needs of NMRAs in developing countries External partners and experts play important role Outcomes are measured by deliverables and indicators of projects funded to PQP and QSM

Thank you for the attention smidm@who.int